Induction of Regulatory T Cells as a Novel Mechanism Underlying the Therapeutic Action of Kakkonto, a Traditional Japanese Herbal Medicine, in a Murine Food Allergy Model
Induction of Regulatory T Cells as a Novel Mechanism Underlying the Therapeutic Action of Kakkonto, a Traditional Japanese Herbal Medicine, in a Murine Food Allergy Model
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DOI：
10.1159/000445433
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发表时间：
2016-06-01
影响因子：
2.8
通讯作者：
Kadowaki, Makoto
中科院分区：
文献类型：
--
作者：
Yamamoto, Takeshi;Fujiwara, Kanae;Kadowaki, Makoto
背景：食物过敏（FA）患者的数量急剧增加。虽然没有令人满意的药物治疗FA，我们已经发现，kakkonto，一种传统的日本草药，抑制过敏症状的发生在FA小鼠模型。因此，我们研究了kakkonto是否可以调节结肠中T细胞的活化和分化。方法：BALB/c小鼠全身致敏，经口给予卵清蛋白攻击。用kakkonto口服处理FA小鼠。分离并分析来自其结肠的固有层（LP）细胞。结果如下：Kakkonto显著降低LP CD 4（+）T细胞中CD 69（+）细胞的比例和升高的辅助T细胞2型特异性转录因子加塔-3 mRNA表达，表明Kakkonto对FA小鼠结肠的LP效应CD 4（+）T细胞的活化和Th 2分化具有抑制作用。此外，kakkonto显著增加FA小鼠结肠LP CD 4（+）T细胞中Foxp 3（+）CD 4（+）调节性T细胞的比例。同样，Foxp 3阳性细胞的数量显着增加，在结肠粘膜的kakkonto管理FA小鼠。然而，在FA模型中给予抗CD 25单克隆抗体并没有减弱kakkonto的药理学作用和Foxp 3（+）CD 4（+）调节性T细胞诱导能力。结论：结肠中Foxp 3（+）CD 4（+）CD 25（-）调节性T细胞的诱导作为kakkonto治疗作用的新机制可用于开发新的抗FA药物。(C)2016 S. Karger AG，巴塞尔
Background: The number of patients with food allergy (FA) has dramatically increased. Although satisfactory drug therapies for FA are not available, we have found that kakkonto, a traditional Japanese herbal medicine, suppressed the occurrence of allergic symptoms in an FA mouse model. Thus, we investigated whether kakkonto could regulate the activation and differentiation of T cells in the colon. Methods: BALB/c mice were systemically sensitized and then orally challenged with ovalbumin. FA mice were orally treated with kakkonto. Lamina propria (LP) cells from their colons were isolated and analyzed. Results: Kakkonto significantly reduced the proportion of CD69(+) cells and the elevated helper T cell type 2-specific transcription factor GATA-3 mRNA expression in the LP CD4(+) T cells, showing that kakkonto has a suppressive effect on the activation and Th2 differentiation of LP effector CD4(+) T cells of the FA mouse colon. Furthermore, kakkonto significantly increased the proportion of Foxp3(+)CD4(+) regulatory T cells in the LP CD4(+) T cells of the FA mouse colon. Similarly, the number of Foxp3-positive cells was dramatically increased in the colonic mucosa of kakkonto-administered FA mice. However, the pharmacological effect and Foxp3(+)CD4(+) regulatory T cell-inducing ability of kakkonto were not attenuated by the administration of an anti-CD25 monoclonal antibody in the FA model. Conclusions: The induction of Foxp3(+)CD4(+)CD25(-) regulatory T cells in the colon as a novel mechanism underlying the therapeutic action of kakkonto could be utilized for the development of a novel anti-FA drug. (C) 2016 S. Karger AG, Basel